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Peripheral mechanisms underlying electroacupuncture analgesia in a rat model of c

电针镇痛大鼠模型的外周机制

基本信息

批准号：
7994815
负责人：
Xuan-Zheng Peter Shi
金额：
$ 18.93万
依托单位：
UNIVERSITY OF TEXAS MED BR GALVESTON
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-12-01 至 2012-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7994815
关键词：
Abdominal Pain Absence of pain sensation Absenteeism Acetic Acids Acupuncture procedure Acute Adult Afferent Neurons Analgesics Attenuated Birth Chronic Clinical Colon Colorectal Consultations Cystathionine Data Disease Electroacupuncture Enzymes Experimental Models Future Gastrointestinal Diseases Gene Expression Habits Healthcare Hydrogen Sulfide Hyperalgesia Hypersensitivity Impairment Inflammatory Injection of therapeutic agent Intestines Irritable Bowel Syndrome Knowledge Lead Marketing Mediating Medical Modality Modeling Molecular Neonatal Neurons Nociceptors Opiates Opioid Pain Pathway interactions Patients Peripheral Pharmaceutical Preparations Physicians Rattus Recurrence Role Safety Signal Pathway Signal Transduction Site Spinal Ganglia Staging Symptoms Syndrome Testing Treatment Effectiveness Visceral Visceral pain Workplace base colorectal distension desensitization economic cost nociceptive response public health relevance receptor success

项目摘要

DESCRIPTION (provided by applicant): Irritable Bowel Syndrome (IBS) remains a common and challenging syndrome for clinicians. It is defined by recurrent symptoms of abdominal pain or discomfort associated with alterations in bowel habits, in the absence of a detectable structural or inflammatory change in the colon. The pain, discomfort, and impairment from IBS often lead to healthcare medical consultation and workplace absenteeism, and associated economic costs. The causes of IBS and effectiveness of treatment have remained elusive. Although opiates have remained to be the drugs of choice for treating patients with severe pain and a few receptor modulators are marketed for treatment of IBS in recent years, there has been concern about the safety of these drugs. Electroacupuncture (EA), a complementary modality, has been used extensively for treatment of various painful conditions and gastrointestinal diseases. The mechanisms of acupuncture are not well understood, however, and one of the major problems impeding this understanding is a lack of proper experimental models. Recently, we have developed a model of EA-induced analgesia in rats with chronic visceral hyperalgesia (CVH). The objective of this application is to evaluate the effect of EA visceral anti- hyperalgesia and its mechanism in a rat model of CVH. We hypothesize that EA reverses the enhanced excitability of colon specific primary sensory neurons which is at least in part mediated by inhibition of endogenous hydrogen sulfide signaling, thus alleviates CVH. To test this hypothesis, we propose the following specific aims: Specific Aim 1 is to evaluate the acute and short-term effects of EA on nociceptive responses to colorectal distention in rats with CVH; Specific Aim 2 is to determine ionic and molecular basis for EA-mediated desensitization of primary sensory neurons in rats with CVH; and Specific Aim 3 is to determine the role of H2S signaling pathway in EA-mediated analgesia in rats with CVH. We believe that our studies on cellular activity, gene expression, and enzymatic activity in peripheral sensory neurons may open new era towards ionic and molecular understanding of EA treatment in CVH. This added knowledge will provide physicians with an increased clinical acceptance of EA in patients with functional bowel diseases. PUBLIC HEALTH RELEVANCE: Chronic visceral hyperalgesia occurs frequently in patients with functional bowel diseases and has not been controlled adequately. Electroacupuncture has been used for millennia to treat pain. This study will evaluate the effects and mechanisms of electroacupuncture on such pain in a rat model of chronic visceral hypersensitivity and the success of the proposed study will greatly advance the management of chronic visceral pain.

描述（由申请人提供）：肠易激综合症（IBS）对于临床医生来说仍然是一种常见且具有挑战性的综合症。它的定义是在结肠中没有可检测到的结构或炎症变化的情况下，与排便习惯改变相关的反复出现的腹痛或不适症状。 IBS 带来的疼痛、不适和损害通常会导致医疗咨询和工作场所缺勤，以及相关的经济成本。 IBS 的病因和治疗效果仍然难以捉摸。尽管阿片类药物仍然是治疗重度疼痛患者的首选药物，并且近年来有一些受体调节剂上市用于治疗肠易激综合症，但人们对这些药物的安全性表示担忧。电针（EA）是一种补充疗法，已广泛用于治疗各种疼痛病症和胃肠道疾病。然而，针灸的机制尚不清楚，阻碍这种理解的主要问题之一是缺乏适当的实验模型。最近，我们在患有慢性内脏痛觉过敏（CVH）的大鼠中开发了一种电针诱导镇痛的模型。本申请的目的是评估 EA 内脏抗痛觉过敏的效果及其在 CVH 大鼠模型中的机制。我们假设 EA 逆转了结肠特异性初级感觉神经元的兴奋性增强，这种兴奋性至少部分是通过抑制内源性硫化氢信号传导介导的，从而减轻了 CVH。为了检验这一假设，我们提出以下具体目标：具体目标 1 是评估 EA 对 CVH 大鼠结直肠扩张的伤害性反应的急性和短期影响；具体目标 2 是确定 CVH 大鼠初级感觉神经元 EA 介导脱敏的离子和分子基础；具体目标3是确定H2S信号通路在EA介导的CVH大鼠镇痛中的作用。我们相信，我们对周围感觉神经元细胞活性、基因表达和酶活性的研究可能会为 CVH 中 EA 治疗的离子和分子理解开辟新纪元。这些增加的知识将使医生提高功能性肠病患者对 EA 的临床接受度。公众健康相关性：功能性肠病患者经常发生慢性内脏痛觉过敏，并且尚未得到充分控制。电针疗法用于治疗疼痛已有数千年历史。这项研究将评估电针对慢性内脏过敏大鼠模型中此类疼痛的作用和机制，该研究的成功将极大地推进慢性内脏疼痛的治疗。